Enhanced formation of free radicals of oxygen may explain many of the deleterious effects of exposure to high concentrations of this gas. The extreme reactivity of these molecules contributes to molecular damage characteristics of oxygen poisoning. A number of studies have shown that the superoxide dismutases may protect against oxygen toxicity by dismuting the superoxide free radical. Our laboratory has concentrated on determining the role of the superoxide dismutases in the development of oxygen adaptation in the adult rat. Biochemical studies have shown that both the copper-zinc and manganese containing superoxide dismutases are increased in activity in the lungs of oxygen adapted rats. Qualitative and quatitative pathological studies have precisely defined the changes in cell mass occurring in the lungs of these animals, and we have found evidence suggesting that hypertrophy of endothelial cells is an essential part of the process of adaptation. This proposal is for funds to develop and apply immunological techniques to localize the superoxide dismutases in intact lung tissue. These techniques are being used to define the cellular distribution of these enzymes in lungs and to define the subcellular localization of both superoxide dismutases. Molecular immunocytochemistry, accomplished by combining morphometric, biochemical and immunocytochemical techniques on a single model will be done to quantitate the changes in cellular and subcellular distribution of these enzymes after hyperoxic exposures.